Adherence to core type 2 diabetes mellitus (T2DM) treatment behaviors is suboptimal, and nonadherence is generally not limited to one treatment behavior. The internet holds promise for programs that aim to improve adherence. We developed a computer-tailored eHealth program for patients with T2DM to improve their treatment adherence, that is, adherence to both a healthy lifestyle and medical behaviors.

The objective of this study is to examine the effectiveness of the eHealth program in a randomized controlled trial.

Patients with T2DM were recruited by their health professionals and randomized into either the intervention group, that is, access to the eHealth program for 6 months, or a waiting-list control group. In total, 478 participants completed the baseline questionnaire, of which 234 gained access to the eHealth program. Of the 478 participants, 323 were male and 155 were female, the mean age was 60 years, and the participants had unfavorable BMI and HbA

levels on average. Outcome data were coll664.

Netherlands Trial Register NL664; https//www.trialregister.nl/trial/6664.R-loops are three-stranded nucleic acid structures with essential roles in many nuclear processes. However, their unchecked accumulation is associated with genome instability and is observed in neurodevelopmental diseases and cancers. Genome-wide profiling of R-loops in normal and diseased cells can help identify locations of pathogenic R-loops and advance efforts to attenuate them. We present an antibody-independent R-loop detection strategy, BisMapR, that combines nuclease-based R-loop isolation with non-denaturing bisulfite chemistry to produce genome-wide profiles that retain strand information. BisMapR achieves greater resolution and is faster than existing strand-specific R-loop profiling strategies. In mouse embryonic stem cells, we apply BisMapR to find that gene promoters form R-loops in both directions and uncover a subset of active enhancers that, despite being bidirectionally transcribed, form R-loops exclusively on one strand. BisMapR reveals a previously unnoticed feature of active enhancers and provides a tool to systematically examine their mechanisms in gene expression.To assemble a brain, differentiating neurons must make proper connections and establish specialized brain compartments. Abnormal levels of cell adhesion molecules disrupt these processes. Dystroglycan (Dg) is a major non-integrin cell adhesion receptor, deregulation of which is associated with dramatic neuroanatomical defects such as lissencephaly type II or cobblestone brain. The previously established Drosophila model for cobblestone lissencephaly was used to understand how Dg is regulated in the brain. During development, Dg has a spatiotemporally dynamic expression pattern, fine-tuning of which is crucial for accurate brain assembly. In addition, mass spectrometry analyses identified numerous components associated with Dg in neurons, including several proteins of the exocyst complex. Data show that exocyst-based membrane trafficking of Dg allows its distinct expression pattern, essential for proper brain morphogenesis. Further studies of the Dg neuronal interactome will allow identification of new factors involved in the development of dystroglycanopathies and advance disease diagnostics in humans.SARS-CoV-2 is difficult to contain because many transmissions occur during pre-symptomatic infection. Unlike influenza, most SARS-CoV-2-infected people do not transmit while a small percentage infect large numbers of people. We designed mathematical models which link observed viral loads with epidemiologic features of each virus, including distribution of transmissions attributed to each infected person and duration between symptom onset in the transmitter and secondarily infected person. We identify that people infected with SARS-CoV-2 or influenza can be highly contagious for less than 1 day, congruent with peak viral load. GSK2656157 SARS-CoV-2 super-spreader events occur when an infected person is shedding at a very high viral load and has a high number of exposed contacts. The higher predisposition of SARS-CoV-2 toward super-spreading events cannot be attributed to additional weeks of shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks, likely due to aerosolization.The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here, we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis.Cancer patients often harbor occult metastases, a potential source of relapse that is targetable only through systemic therapy. Studies of this occult fraction have been limited by a lack of tools with which to isolate discrete cells on spatial grounds. We developed PIC-IT, a photoconversion-based isolation technique allowing efficient recovery of cell clusters of any size – including single-metastatic cells – which are largely inaccessible otherwise. In a murine pancreatic cancer model, transcriptional profiling of spontaneously arising microcolonies revealed phenotypic heterogeneity, functionally reduced propensity to proliferate and enrichment for an inflammatory-response phenotype associated with NF-κB/AP-1 signaling. Pharmacological inhibition of NF-κB depleted microcolonies but had no effect on macrometastases, suggesting microcolonies are particularly dependent on this pathway. PIC-IT thus enables systematic investigation of metastatic heterogeneity. Moreover, the technique can be applied to other biological systems in which isolation and characterization of spatially distinct cell populations is not currently feasible.